Neuroimmune and behavioral changes elicited by maternal immune activation in mice are ameliorated by early postnatal immune stimulation.

Though the etiology of autism spectrum disorder (ASD) is complex and not fully understood, it is believed that genetic risk factors, coupled with early life inflammation may predispose individuals to develop ASD. Maternal immune activation (MIA) is associated with increased incidence of ASD in offspring; however, not all mothers who experience inflammation during pregnancy have children with autism, suggesting that MIA may act as a disease primer that results in ASD pathology when paired with additional inflammatory insults. Here, we tested the hypothesis that MIA is a disease primer by using a two-hit model that combined MIA with a secondary immune stimulation in early life.

Comparison of the multivariate genetic architecture of eight major psychiatric disorders across sex.

Differences in the patterning of genetic sharing between groups of individuals may arise from biological pathways, social mechanisms, phenotyping and ascertainment. We expand genomic structural equation modeling to allow for testing genomic structural invariance (GSI), that is, the formal comparison of multivariate genetic architecture across groups. We apply GSI to compare the autosomal multivariate genetic architecture of eight psychiatric disorders spanning three factors (psychotic, neurodevelopmental and internalizing) between cisgender males and females.

From Negative to No Cooperativity: Effects of Mutations on Intersubunit Communication within FH:NADP Oxidoreductase Using Steady-State and Pre-Steady-State Kinetic Methods.

FH:NADP oxidoreductase (Fno) catalyzes the reversible production of NADPH by transferring a hydride from the reduced F cofactor to NADP. Previous kinetic studies suggest that wild-type Fno (Fno) displays half-site reactivity and negative cooperativity, making Fno regulatory within methanogenic and sulfate-reducing archaea. These studies identified four amino acids; R186, T192, S190, and H133, as potential candidates involved in intersubunit communication due to their location either at or within close proximity to the interface of the dimer.

Type 2 diabetes polygenic risk score demonstrates context-dependent effects and associations with type 2 diabetes-related risk factors and complications across diverse populations.

Polygenic risk scores (PRS) hold prognostic value for identifying individuals at higher risk of type 2 diabetes (T2D). However, further characterization is needed to understand the generalizability of T2D PRS in diverse populations across various contexts. We characterized a multi-ancestry T2D PRS among 244,637 cases and 637,891 controls across eight populations from the Population Architecture Genomics and Epidemiology (PAGE) Study and 13 additional biobanks and cohorts.